Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Eur Respir J. 2024 Sep 12;64(3). doi: 10.1183/13993003.00512-2024. Print 2024 Sep.
Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma.
Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed.
46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively.
Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.
本那鲁单抗可快速且几乎完全耗尽血液和肺组织中的嗜酸性粒细胞。我们研究了本那鲁单抗是否可以减轻过敏性哮喘患者的变应原诱导的晚期哮喘反应(LAR)。
筛选时痰液嗜酸性粒细胞增多且存在 LAR 的过敏性哮喘患者被随机分为本那鲁单抗 30mg 或匹配的安慰剂组,每组 23 例,每 4 周给药 1 次,共 8 周(3 剂)。在第 9 周和第 12 周进行变应原挑战,评估血液、痰液、骨髓和支气管组织嗜酸性粒细胞和 LAR。
46 名参与者(平均年龄 30.9 岁)被随机分为本那鲁单抗组(n=23)或安慰剂组(n=23)。与安慰剂组相比,本那鲁单抗组在治疗开始后 4 周时血液中、9 周时痰液和骨髓中嗜酸性粒细胞显著减少。在第 9 周变应原挑战后 7 小时,与安慰剂组相比,本那鲁单抗组痰液嗜酸性粒细胞增多明显减轻(最小二乘均数差值-5.81%,95%CI-10.69-0.94%;p=0.021);然而,LAR 无显著差异(最小二乘均数差值 2.54%,95%CI 3.058.12%;p=0.363)。本那鲁单抗组和安慰剂组分别有 7(30.4%)例和 14(60.9%)例报告不良事件。
在 8 周的时间内给予本那鲁单抗可显著减轻轻度过敏性哮喘患者的血液、骨髓和痰液嗜酸性粒细胞;然而,LAR 没有变化,这表明嗜酸性粒细胞本身并不是变应原诱导的支气管收缩的关键组成部分。